Optogenetic rewiring of thalamocortical circuits to restore function in the stroke injured brain

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dc.contributor.authorTennant, Kelly A.
dc.contributor.authorTaylor, Stephanie L.
dc.contributor.authorWhite, Emily R.
dc.contributor.authorBrown, Craig E.
dc.date.accessioned2018-08-27T14:38:36Z
dc.date.available2018-08-27T14:38:36Z
dc.date.copyright2017en_US
dc.date.issued2017
dc.description.abstractTo regain sensorimotor functions after stroke, surviving neural circuits must reorganize and form new connections. Although the thalamus is critical for processing and relaying sensory information to the cortex, little is known about how stroke affects the structure and function of these connections, or whether a therapeutic approach targeting these circuits can improve recovery. Here we reveal with in vivo calcium imaging that stroke in somatosensory cortex dampens the excitability of surviving thalamocortical circuits. Given this deficit, we hypothesized that chronic transcranial window optogenetic stimulation of thalamocortical axons could facilitate recovery. Using two-photon imaging, we show that optogenetic stimulation promotes the formation of new and stable thalamocortical synaptic boutons, without impacting axon branch dynamics. Stimulation also enhances the recovery of somatosensory cortical circuit function and forepaw sensorimotor abilities. These results demonstrate that an optogenetic approach can rewire thalamocortical circuits and restore function in the damaged brain.en_US
dc.description.reviewstatusRevieweden_US
dc.description.scholarlevelFacultyen_US
dc.description.sponsorshipThe authors thank Kerry Delaney, Gautam Awatramani, Patrick Reeson and Eslam Mehina for technical advice and critical feedback on the manuscript. We are grateful to the scientists of the Genetically-Encoded Neuronal Indicator and Effector (GENIE) Project at the Janelia Farm Research Campus of the Howard Hughes Medical Institute and Dr Karl Deisseroth of Stanford University for generously allowing GCaMP6 and ChR2 viral constructs to be distributed through the Penn State Vector Core. This work was supported by operating, salary and equipment grants to C.E.B. from the Canadian Institutes of Health Research (CIHR), Heart and Stroke Foundation (HSF), Michael Smith Foundation for Health Research (MSFHR) and Natural Sciences and Engineering Research Council of Canada (NSERC). K.A.T. was supported by postdoctoral fellowships from the CIHR and the Canadian Diabetes Association.en_US
dc.identifier.citationTennant, K.A.; Taylor, S.L.; White, E.R.; & Brown, C.E. (2017). Optogenetic rewiring of thalamocortical circuits to restore function in the stroke injured brain. Nature Communications, 8(15879). https://doi.org/10.1038/ncomms15879en_US
dc.identifier.urihttps://doi.org/10.1038/ncomms15879
dc.identifier.urihttp://hdl.handle.net/1828/9960
dc.language.isoenen_US
dc.publisherNature Communicationsen_US
dc.subject.departmentDivision of Medical Sciences
dc.subject.departmentSchool of Medical Sciences
dc.subject.departmentDepartment of Biology
dc.titleOptogenetic rewiring of thalamocortical circuits to restore function in the stroke injured brainen_US
dc.typeArticleen_US

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